This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Diabetic Retinopathy (retinal eye disease, DR) is the leading cause of blindness in people aged 20-74 years in the United States. Although retinopathy is more common in type 1 diabetes, the majority of new cases are due to type 2 diabetes (T2DM). Severe forms of DR occur only, however, in approximately one-third of patients, i.e., a subgroup that appears to be genetically predisposed to progressive disease. Although other factors also play a role in the development of DR, such as glucose control and high blood pressure, this proposal will focus on studying genetics of DR. The Hispanic population will be studied in this grant because Latinos have a strong propensity for development of both T2DM and DR. This proposal is a joint effort among three centers: LA Biomed, which is the Clinical Phenotyping Center, the University of Wisconsin, which houses the Ocular Epidemiology Reading Center and Cedars-Sinai Medical Center, where the genetic testing will be done. We will peform a genome-wide search to identify candidate regions in the genome that may be linked with DR. Non-parametric sib-pair linkage analysis and variance components linkage analysis will be utilized to identify regions that may contain genes contributing to DR. Successful completion of this project is anticipated to result in the initial phase in locating novel gene(s) that confer susceptibility to DR. Characterization of the products of these genes will enhance our understanding of the pathogenesis of DR and has the potential to lead to the development of new preventive and therapeutic strategies.